Simultaneous Fluorescence Imaging Reveals N-Methyl-d-aspartic Acid Receptor Dependent Zn2+/H+ Flux in the Brains of Mice with Depression

Abstract

Depression is immensely attributed to the overactivation of N-methyl-d-aspartic acid (NMDA) receptor in the brains. As regulatory binding partners of NMDA receptor, both Zn²⁺ and H⁺ are intimately interrelated to NMDA receptor's activity. Therefore, exploring synergistic changes on the levels of Zn²⁺ and H⁺ in brains will promote the knowledge and treatment of depression. However, the lack of efficient, appropriate imaging tools limits simultaneously tracking Zn²⁺ and H⁺ in living mouse brains. Thus, a well-designed dual-color fluorescent probe (DNP) was fabricated for the simultaneous monitoring of Zn²⁺ and H⁺ in the brains of mice with depression. Encountering Zn²⁺, the probe evoked bright blue fluorescence at 460 nm. Meanwhile, the red fluorescence at 680 nm was decreased with H⁺ addition. With blue/red dual fluorescence signal of DNP, we observed the synchronous increased Zn²⁺ and H⁺ in PC12 cells under oxidative stress. Notably, in vivo imaging for the first time revealed the simultaneous reduction of Zn²⁺ and pH in brains of mice with depression-like behaviors. Further results implied that the NMDA receptor might be responsible for the coinstantaneous fluctuation of Zn²⁺ and H⁺ during depression. Altogether, this work is conducive to the knowledge of neural signal transduction mechanisms, advancing our understanding of the pathogenesis in depression.